• Journal of Society of Preventive Korean Medicine
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• v.17 no.1
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• pp.77-88
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• 2013

Objectives : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. Methods : After 10mg/kg of donepezil treatment, Gongjindan 100mg/kg was administered within 5 min. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of Gongjindan treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. PK parameters of donepezil were analysis as compared with donepezil single administered rats. Results : Gongjindan markedly inhibited the absorption of donepezil regardless of sample time, from 30min to 8hrs after end of co-administration comparing with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2hrs after co-administration as compared with donepezil single treated rats, in the present study. Accordingly, the Cmax(-27.76%), $AUC_{0-t}$(-27.22%) and $AUC_{0-inf}$(-26.54%) of donepezil in co-administered rats were significantly decreased as compared with donepezil single treated rats, respectively. Conclusions : Based on the results of the present study, co-administration of Gongjindan decreases the oral bioavailability of donepezil by inhibiting the absorption. It is considered that the more detail pharmacokinetic studies should betested to conclude the effects of Gongjindan on the pharmacokinetics of donepezil, when they were co-administered, like the effects after co-administration with reasonable intervals considering the Tmax of donepezil and after repeated co-administrations.

• Korean Journal of Environmental Biology
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• v.42 no.1
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• pp.54-61
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• 2024

The ecosystem provides a diverse array of environmental conditions for organisms, and only those that are capable of successfully adapting to these conditions within their habitats can endure, thrive, and proliferate. Further, the environmental conditions within these habitats can significantly affect the bioavailability of chemicals that are introduced therein, thus resulting in varied adverse impacts on the organisms. The present study aims to evaluate the sensitivity of Yuukianura szeptyckii - a species adapted to riparian - to heavy metals following ISO guideline 11276, with the objective of assessing its potential as an indicator species for ecotoxicological evaluations in riparian habitats. The findings revealed that cadmium and copper both had significant toxic effects depending on their concentrations. For cadmium, the LC₅₀ was 280 mg kg^-1, EC₅₀ was 66 mg kg^-1, and NOEC and LOEC were 25 and 50 mg kg^-1, respectively. For copper, the LC₅₀ was 911 mg kg^-1, EC₅₀ was 151 mg kg^-1, and LOEC was 50 mg kg^-1. Comparative analysis with previous results for the international standard species Folsomia candida and the domestic standard species Allonychiurus kimi indicated that Y. szeptyckii exhibited even greater sensitivity to toxicity values. The adverse effects on survival and reproduction were closely associated with the influx concentration of heavy metals in their bodies. Altogether, the results suggest that Y. szeptyckii is a sensitive species for ecotoxicological assessments in riparian habitats, thus making it suitable as an indicator species, particularly in riparian ecosystems that are characterized by relatively high humidity conditions.

• Journal of Life Science
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• v.28 no.5
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• pp.605-614
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• 2018

Bee pollen has an outer wall which is resistant to both acidic and basic solutions and even the digestive enzymes in the gastrointestinal tract. Therefore, the oral bioavailability of bee pollen is only 10-15%. A previous study reported on wet-grinding technology which increased the extraction of active ingredients from bee pollen by 11 times. This study was designed to investigate the safety of wet-ground bee pollen. First, a single dose of wet-ground bee pollen was tested in both rats and beagle dogs at dosages of 5, 10, and 20 g/kg and 1.5, 3, and 6 g/kg, respectively. In rats, compound-colored stools were found in those administered 10 g/kg or more of wet-ground bee pollen. In beagle dogs, 6 g/kg of wet-ground bee pollen induced diarrhea in one male for four hours. However, no obvious clinical signs were found through the end of the experiment in rats and beagle dogs. In addition, no histological abnormality was found in all animals. The data indicates that a single dose of up to 20 g/kg of wet-ground bee pollen is safe. Next, the genetic toxicity of nano-sized bee pollen was tested. This study employed a bacterial reverse mutation test, a micronucleus assay, and a chromosomal aberration assay. In the micronucleus assay, there was no genetic toxicity up to the dosage of 2 g/kg. There was also no genetic toxicity in the bacterial reverse mutation test and chromosomal aberration assay. This data provides important information in developing nano-sized bee pollen into more advanced functional foods and herbal medicines.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8377-8382
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• 2014

Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1-oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells.

• Journal of Life Science
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• v.34 no.4
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• pp.215-226
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• 2024

Aralia continentalis is widely distributed in Far East Asian countries such as Korea, China, and Japan. A. continentalis has traditionally been used as an herbal remedy for various conditions, including analgesia, headache, inflammation, lameness, lumbago, rheumatism, and dental diseases in Korea. Previously, epi-continentalic acid, continentalic acid, and kaurenoic acid as major active biological compounds belonging to the diterpenoid class were identified. To synthesize diterpenoid derivatives with enhanced bioavailability, Fusarium fujikuroi was employed to biotransform diterpenoids due to its known antibacterial activity. This yielded two derivatives of kaurenoic acid, namely 16α-hydroxyent-kauran-2-on-19-oic acid and 2β, 16α-dihydroxy-ent-kauran-19-oic acid, with their chemical structures elucidated via NMR analysis. These derivatives exhibited increased polarity compared to kaur- enoic acid, as evidenced by their retention time on preparative HPLC using the ODS-A column and structural modifications. Evaluation of their antidiabetic activity targeting PTP1B, a negative regulator of the insulin signaling pathway, revealed inhibitory activities of 30.8% and 27.6%, respectively, at a concentration of 4 ㎍/ml. Additionally, both derivatives demonstrated low cytotoxicity, with an IC50 value 18 times higher than kaurenoic acid. Therefore, the augmented water solubility and reduced toxicity of 16α-hydroxy-ent-kauran-2-on-19-oic acid and 2β, 16α-dihydroxy-ent-kauran-19-oic acid, resulting from biotransformation by F. fujikuroi, render them promising candidates for industrial applications.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.911-920
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• 2006

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

• Polymer(Korea)
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• v.33 no.2
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• pp.111-117
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• 2009

This study aims to verify for humans the suitability of the enzyme-fixed hydrogel used for the patch sensor of the blood sugar testing system without blood sampling, which utilizes reverse iontophoresis. Using acrylate monomers, hydrogel was synthesized to which a certain unit of enzyme is fixed. In order to analyze the material property of the synthesized hydrogel, a structural analysis was performed using FT-IR spectroscopy, while the DSC was used to verify the thermal stability. In addition, with the UV-Vis spectrophotometer, it was verified that the degree of active enzyme is at least 50% greater than the standard product. The SEM was used to verify secure fixation of the enzyme onto the surface. As a result, it was observed that the enzyme is successfully fixed to the surface. Since the hydrogel makes direct contact with a patient's skin, it is essential to evaluate the toxicity when making direct contact with the skin. For that purpose, various sets of tests were undertaken according to the ISO 10993-cytotoxicity, intracutaneous reactivity, skin irritation test and maximization sensitization. Consequently, it was successfully verified that the enzyme-fixed hydrogel have bioavailability.